Osmotic dispensing devices for delivery of therapeutically active agents are well known in the art. Such devices use an expansion means to deliver an agent to an environment of use over a period of hours, days or months. The expansion means absorbs liquid, expands, and acts to drive out beneficial agent formulation from the interior of the device in a controlled, usually constant manner. The osmotic expansion means is used to controllably, usually relatively slowly, and over a period of time, deliver the agent. Thus, these devices are not generally used to delay the initial release of the agent, followed by the rapid release, or substantially simultaneous introduction, of all of the agent or all of the dosage form(s) containing the agent into the environment of use at one time.
The delay of the initial release of an agent has primarily been previously effected by coating the agent or a formulation containing the agent with a dissolvable or bioerodible coating layer, such as gelatin, which coating dissolves or erodes in the environment of use to then make the agent available. Delayed initial release has also been provided by dispersing the agent in a dissolvable or erodible matrix. However, such systems are often unreliable and release cannot be controlled with great accuracy due to the variability and relatively uncontrollable nature of erosion and dissolution.
PCT publication WO 90/09168 discloses an oral delivery capsule having two pieces, one of which is a plug made of a water-sensitive material. A delay in the initial release of an agent is provided by the plug taking up water, resulting in the plug swelling or expanding and eventually separating from the body of the capsule to allow release of the agent contained within. Unfortunately, the swelling and eventual release of the plug causes the volume inside the capsule to expand, which creates a vacuum within the capsule that causes fluid from the fluid environment to enter the capsule and come into contact with the active agent. When the active agent is sensitive to fluids, as are certain proteins and peptides, such contact can cause agglomeration or inactivation of the agent. Additionally, the fluid taken up by the swelling water-sensitive plug also can come into contact with fluid-sensitive active agents.
Therefore, there remains a continuing need for improved methods and systems for providing a delayed initial delivery of an active agent to an environment of use that are reliable and that can be programmed to deliver the agent after a particular interval with increased accuracy and while protecting sensitive active agents.